Colonic DiseasesPhase 2NCT00201331
Prospective Phase II Randomized Trial of Postoperative Adjuvant Chemotherapy in Patients With High Risk Colon Cancer
A Phase 2 study testing leucovorin+5-FU in people with Colonic Diseases and Adenocarcinoma, run by National Health Research Institutes, Taiwan at 1 site in Taiwan.
Trial summary
Based on the astonishing high response rate in metastatic colorectal cancer in weekly high dose 5-FU and leucovorin, we will conduct a clinical trial to clarify the activity of this regimen in the adjuvant setting. Read more about this study
- Who is it for?
- Ages 18 to 70 years
- Conditions the study is for
- Colonic Diseases, Adenocarcinoma
- What is being tested?
- leucovorin+5-FU
- How many people
- 162 participants
- Where
- 1 siteTaiwan
- Study dates
- Apr 2002to Oct 2012
- Phase
- Phase 2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 70 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Signed written informed consent. Curative resection of colon cancer and upper rectal cancer, which is not planned for radiotherapy. Histologically proved adenocarcinoma of the colon. Stages: T1-4N2M0 (LN ≧4) Age less or equal to 70 years old. Performance status: 0 to 1 (ECOG) Adequate liver function (Bil. < 2 mg/dl, GOT, GPT< 3x normal limit) Adequate renal function (Cr < 2.0 mg/dl) Adequate bone marrow function(WBC ≧3500/mm3, Platelet ≧100000/mm3) Individual regular follow-up possible. 3.320 Patient who can receive adjuvant chemotherapy within 6 weeks after operation.
- Patient who can receive a "indwelling catheter" surgery.
Who cannot join
- Uncontrolled intercurrent illness, e.g. active infection or concurrent major systemic disease (e.g. psychosis, ESRD, heart failure [NYHA class III], liver cirrhosis [Child B\&C], or AIDS). Intestinal obstruction or occlusion postoperation. Pregnant or lactating woman. Allergy to 5-Fluorouracil or leucovorin. Other primary cancer except skin squamous or basal cell carcinoma or cured in-situ cancer of the cervix.
- Previous treatment of chemotherapy or radiotherapy.
Trial locations and contacts
1 site in 1 country.
Taiwan1 site, 1 recruiting
- Recruiting
Chang Gung Memorial Hospital
Taoyuan, 333
Tsai-Sheng Yang, MD, 886-3-3281200 ext. 2114, a481124@adm.cgmh.org.tw
About this study
Based on the astonishing high response rate in metastatic colorectal cancer in weekly high dose 5-FU and leucovorin, we will conduct a clinical trial to clarify the activity of this regimen in the adjuvant setting. The regimen of 5-FU and high dose leucovorin administered as the schedule of INT-0089 will be chosen as the controlled arm which was proven as effective as standard 5-FU plus levamisole regimen with short duration of treatment.21 In this study, continuous infusion of 5-FU (HDFL, Arm B) and bolus injection of 5-FU (Arm A) will be administered to the high risk colon cancer(N2 disease) patients. The role of TS level and inhibition of TS as a predictor of adjuvant chemotherapy with 5-FU based treatment will be clearly defined prospectively.
Read the detailed description
Approximately 75% of all patients with colon carcinoma present at a stage when all gross tumor can be surgically resected. Despite that high resectability rate, about 50% of all colon adenocarcinoma patients die of subsequent metastatic disease not apparent at surgery. These individuals could benefit from adjuvant local or systemic chemotherapy.
Based on the encouraging antitumor activity of 5-FU plus leucovorin(LV) in patients with metastatic colon carcinoma6,7, several investigators reported their results using this combination in the adjuvant setting. Results of an NSABP C-038 suggested that postoperative 5-FU plus leucovorin reduces the risk of colon cancer recurrence by 30% and the associated mortality by 32% compared with MOF(semustine, vincristine, and 5-FU). Recently, investigators from the IMPACT group9 analyzed the role of adjuvant 5-FU plus high dose leucovorin given 5 days every 28 days for a total of six courses versus no treatment in patients with stage II or III colon cancer. The treatment arm showed a significant reduction (by 22%) in mortality (P=0.029) and a 35% reduction in relapse rate (P=0.0001). Preliminary results from other studies have also suggested benefits of 5-FU plus leucovorin as adjuvant treatment of colon cancer10,11,12. Those studies had employed chemotherapy with 5-FU plus leucovorin, although there were differences in duration of treatment and drug dose among those trials, it is striking that all revealed a similar magnitude of benefit for adjuvant chemotherapy with 5-FU and leucovorin in node positive patients. At the present time, both 5-FU plus levamisole and 5-FU plus leucovorin can be considered acceptable adjuvant chemotherapy regimens for patients with node positive disease.
Thymidylate synthase(TS) is a critical therapeutic target for the fluoropyrimidine cytotoxic drugs that are the mainstay of the treatment for patients with advanced colorectal cancer. TS provide the sole de nono source of thymidylate for DNA synthesis. The clinical importance of TS in determining fluoropyrimidine cytotoxicity has been established in both clinical and preclinical study. Increased expression of TS protein due to underlying gene amplification has been described in cell lines selected for drug resistance by exposure to 5-FU.22,23 Several investigators have also demonstrated that intratumoral TS activity are predictive for response to 5-FU.24-26 High TS activity was associated with no response, whereas a low TS activity was associated with good response to 5-FU.
- Conditions
- Colonic Diseases, Adenocarcinoma
- Being tested
- leucovorin+5-FU
- Medical subject headings
- Colonic Diseases, Adenocarcinoma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
leucovorin+5-FUDrug
What is being measured
The primary outcome is the main question the study is designed to answer.
To compare the DFS and OS of HDFL vs. weekly bolus 5-FU plus high dose LV as adjuvant chemotherapy for N2 colon cancer
Secondary outcomes (3)
1. To evaluate safety and toxicity of both arm
2. To assess the impact of TS overexpression on patients with resectable N2 colon carcinoma.
3. To assess the disease-free survival of patients with high or low TS level of N2 colon cancer, when adjuvant chemotherapy of 5-FU was administered by bolus or continuous infusion .
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted20 Sep 2005 (estimated)
- Study startApr 2002
- Study completionOct 2012
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Colonic DiseasesStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 162 participants
Sponsor and investigators
- Lead sponsor
- National Health Research Institutes, Taiwan
- Sponsor type
- University, hospital or other
- Collaborators
- Chang Gung Memorial Hospital, Changhua Christian Hospital, China Medical University Hospital, Mackay Memorial Hospital, Chi Mei Medical Hospital, Kaohsiung Veterans General Hospital., National Cheng-Kung University Hospital, Taichung Veterans General Hospital
- Investigators
- Cheng-Yi Wang, PHD, Study chair, Chang Gung Memorial Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00201331
- Sponsor's protocol ID
- T1202
- Status last verified
- Dec 2005
- First submitted
- 13 Sep 2005
- Last updated
- 16 Dec 2005
- Results posted
- No
Study at a glance
From the registry record, last updated by the sponsor on 16 Dec 2005. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Prospective Phase II Randomized Trial of Postoperative Adjuvant Chemotherapy in Patients With High Risk Colon Cancer
- ClinicalTrials.gov ID
- NCT00201331
- Acronym / sponsor ID
- T1202
- Conditions
- Colonic Diseases, Adenocarcinoma
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 162 participants
- Lead sponsor
- National Health Research Institutes, TaiwanUniversity, hospital or other
- Collaborators
- Chang Gung Memorial Hospital, Changhua Christian Hospital, China Medical University Hospital, Mackay Memorial Hospital, Chi Mei Medical Hospital, Kaohsiung Veterans General Hospital., National Cheng-Kung University Hospital, Taichung Veterans General Hospital
- Study start
- Apr 2002
- Study completion
- Oct 2012
- First posted
- 20 Sep 2005 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Based on the astonishing high response rate in metastatic colorectal cancer in weekly high dose 5-FU and leucovorin, we will conduct a clinical trial to clarify the activity of this regimen in the adjuvant setting. The regimen of 5-FU and high dose leucovorin administered as the schedule of INT-0089 will be chosen as the controlled arm which was proven as effective as standard 5-FU plus levamisole regimen with short duration of treatment.21 In this study, continuous infusion of 5-FU (HDFL, Arm B) and bolus injection of 5-FU (Arm A) will be administered to the high risk colon cancer(N2 disease) patients. The role of TS level and inhibition of TS as a predictor of adjuvant chemotherapy with 5-FU based treatment will be clearly defined prospectively.
Detailed description
Approximately 75% of all patients with colon carcinoma present at a stage when all gross tumor can be surgically resected. Despite that high resectability rate, about 50% of all colon adenocarcinoma patients die of subsequent metastatic disease not apparent at surgery. These individuals could benefit from adjuvant local or systemic chemotherapy.
Based on the encouraging antitumor activity of 5-FU plus leucovorin(LV) in patients with metastatic colon carcinoma6,7, several investigators reported their results using this combination in the adjuvant setting. Results of an NSABP C-038 suggested that postoperative 5-FU plus leucovorin reduces the risk of colon cancer recurrence by 30% and the associated mortality by 32% compared with MOF(semustine, vincristine, and 5-FU). Recently, investigators from the IMPACT group9 analyzed the role of adjuvant 5-FU plus high dose leucovorin given 5 days every 28 days for a total of six courses versus no treatment in patients with stage II or III colon cancer. The treatment arm showed a significant reduction (by 22%) in mortality (P=0.029) and a 35% reduction in relapse rate (P=0.0001). Preliminary results from other studies have also suggested benefits of 5-FU plus leucovorin as adjuvant treatment of colon cancer10,11,12. Those studies had employed chemotherapy with 5-FU plus leucovorin, although there were differences in duration of treatment and drug dose among those trials, it is striking that all revealed a similar magnitude of benefit for adjuvant chemotherapy with 5-FU and leucovorin in node positive patients. At the present time, both 5-FU plus levamisole and 5-FU plus leucovorin can be considered acceptable adjuvant chemotherapy regimens for patients with node positive disease.
Thymidylate synthase(TS) is a critical therapeutic target for the fluoropyrimidine cytotoxic drugs that are the mainstay of the treatment for patients with advanced colorectal cancer. TS provide the sole de nono source of thymidylate for DNA synthesis. The clinical importance of TS in determining fluoropyrimidine cytotoxicity has been established in both clinical and preclinical study. Increased expression of TS protein due to underlying gene amplification has been described in cell lines selected for drug resistance by exposure to 5-FU.22,23 Several investigators have also demonstrated that intratumoral TS activity are predictive for response to 5-FU.24-26 High TS activity was associated with no response, whereas a low TS activity was associated with good response to 5-FU.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
Who may qualify
- Ages
- 18 to 70 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (2 listed)
- Signed written informed consent. Curative resection of colon cancer and upper rectal cancer, which is not planned for radiotherapy. Histologically proved adenocarcinoma of the colon. Stages: T1-4N2M0 (LN ≧4) Age less or equal to 70 years old. Performance status: 0 to 1 (ECOG) Adequate liver function (Bil. < 2 mg/dl, GOT, GPT< 3x normal limit) Adequate renal function (Cr < 2.0 mg/dl) Adequate bone marrow function(WBC ≧3500/mm3, Platelet ≧100000/mm3) Individual regular follow-up possible. 3.320 Patient who can receive adjuvant chemotherapy within 6 weeks after operation.
- Patient who can receive a "indwelling catheter" surgery.
Key exclusion criteria (2 listed)
- Uncontrolled intercurrent illness, e.g. active infection or concurrent major systemic disease (e.g. psychosis, ESRD, heart failure [NYHA class III], liver cirrhosis [Child B\&C], or AIDS). Intestinal obstruction or occlusion postoperation. Pregnant or lactating woman. Allergy to 5-Fluorouracil or leucovorin. Other primary cancer except skin squamous or basal cell carcinoma or cured in-situ cancer of the cervix.
- Previous treatment of chemotherapy or radiotherapy.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| leucovorin+5-FU | Drug | – |
Primary outcome
To compare the DFS and OS of HDFL vs. weekly bolus 5-FU plus high dose LV as adjuvant chemotherapy for N2 colon cancer
3 secondary outcomes
1. To evaluate safety and toxicity of both arm
2. To assess the impact of TS overexpression on patients with resectable N2 colon carcinoma.
3. To assess the disease-free survival of patients with high or low TS level of N2 colon cancer, when adjuvant chemotherapy of 5-FU was administered by bolus or continuous infusion .
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 16 Dec 2005.
- Related InfoLink provided by the sponsor.
Related trials for Colonic Diseases
Not yet recruitingPhase 1
Hepatic Artery Infusion of Carfilzomib in Participants With Liver Metastatic Disease Previously Treated With Hepatic Artery Infusion Pump Therapy
Colorectal Neoplasms, Neoplasms
Not yet recruitingPhase 1
An Open-label, DDI Study to Investigate the Effects of Duvakitug on the PK of Selected Cytochrome P450 Substrates
Ulcerative Colitis, Crohn's Disease
Active, not recruiting
Streamlined Geriatric and Oncological Evaluation Based On IC Technology
Breast Cancer, Comorbidities and Coexisting Conditions
Enrolling by invitationObservational study
Natural History Study of Early Life Exposures in Agriculture (ELEA)
Prostate Cancer, Leukemia
RecruitingPhase 2
Tislelizumab in People With Colorectal Cancer
Colorectal Cancer
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Cheng-Yi Wang, PHD study chair
Chang Gung Memorial Hospital
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing leucovorin+5-FU in people with Colonic Diseases and Adenocarcinoma, run by National Health Research Institutes, Taiwan at 1 site in Taiwan.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 2 inclusion and 2 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 16 Dec 2005. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Taiwan. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Chiou Mei Liu (886-2-26534401 ext. 25158, michelle@nhri.org.tw), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
To compare the DFS and OS of HDFL vs. weekly bolus 5-FU plus high dose LV as adjuvant chemotherapy for N2 colon cancer. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 16 Dec 2005.